Universität zu Köln

Giersch, Katja, Allweiss, Lena, Volz, Tassilo ORCID: 0000-0003-3120-8958, Helbig, Martina, Bierwolf, Jeanette, Lohse, Ansgar W., Pollok, Joerg M., Petersen, Joerg, Dandri, Maura and Luetgehetmann, Marc (2015). Hepatitis Delta co-infection in humanized mice leads to pronounced induction of innate immune responses in comparison to HBV mono-infection. J. Hepatol., 63 (2). S. 346 - 354. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1600-0641

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Abstract

Background & Aims: The limited availability of hepatitis Delta virus (HDV) infection models has hindered studies of interactions between HDV and infected hepatocytes. The aim was to investigate the antiviral state of HDV infected human hepatocytes in the setting of co-infection with hepatitis B virus (HBV) compared to HBV mono-infection using human liver chimeric mice. Methods: Viral loads, human interferon stimulated genes (hISGs) and cytokines were determined in humanized uPA/SCID/beige (USB) mice by qRT-PCR, ELISA and immunofluorescence. Results: Upon HBV/HDV inoculation, all mice developed viremia, which was accompanied by a significant induction of hISGs (i.e. hISG15, hSTATs, hHLA-E) compared to uninfected mice, while HBV mono-infection led to weaker hISG elevations. In the setting of chronic infection enhancement of innate defense mechanisms was significantly more prominent in HBV/HDV infected mice. Also the induction of human-specific cytokines (hIP10, hTGF-beta, hIFN-beta and hIFN-lambda) was detected in HBV/HDV co-infected animals, while levels remained lower or below detection in uninfected and HBV mono-infected mice. Moreover, despite the average increase of hSTAT levels determined in HBV/HDV infected livers, we observed a weaker hSTAT accumulation in nuclei of hepatocytes displaying very high HDAg levels, suggesting that HDAg may in part limit hSTAT signaling. Conclusions: Establishment of HDV infection provoked a clear enhancement of the antiviral state of the human hepatocytes in chimeric mice. Elevated pre-treatment ISG and interferon levels may directly contribute to inflammation and liver damage, providing a rationale for the more severe course of HDV-associated liver disease. Such antiviral state induction might also contribute to the lower levels of HBV activity frequently found in co-infected hepatocytes. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Giersch, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Allweiss, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Volz, Tassilo UNSPECIFIED orcid.org/0000-0003-3120-8958 UNSPECIFIED Helbig, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Bierwolf, Jeanette UNSPECIFIED UNSPECIFIED UNSPECIFIED Lohse, Ansgar W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pollok, Joerg M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Petersen, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Dandri, Maura UNSPECIFIED UNSPECIFIED UNSPECIFIED Luetgehetmann, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-398160
DOI:	10.1016/j.jhep.2015.03.011
Journal or Publication Title:	J. Hepatol.
Volume:	63
Number:	2
Page Range:	S. 346 - 354
Date:	2015
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1600-0641
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTERFERON-STIMULATED GENE; B-VIRUS; C VIRUS; ALPHA; EXPRESSION; RNA; HEPATOCYTES; REPLICATION; PROTEINS; BINDING Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39816